Gabexate mesilate（GM） is a trypsin inhibitor,and mainly used for treatment of various acute pancreatitis,including traumatic pancreatitis（TP）,edematous pancreatitis,and acute necrotizing pancreatitis. However,due ...Gabexate mesilate（GM） is a trypsin inhibitor,and mainly used for treatment of various acute pancreatitis,including traumatic pancreatitis（TP）,edematous pancreatitis,and acute necrotizing pancreatitis. However,due to the characteristics of pharmacokinetics,the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration,which is difficult to manage. Specially,when the blood supply of pancreas is directly damaged,intravenous administration is difficult to exert the optimum therapy effect. To address it,a novel thermosensitive in-situ gel of gabexate mesilate（GMTI） was developed,and the optimum formulation of GMTI containing 20.6%（w/w） P-407 and 5.79%（w/w） P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro,and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin（HE） staining,and its curative effect on grade Ⅱ pancreas injury was also evaluated by testing amylase（AMS）,C-reactive protein（CRP） and trypsinogen activation peptide（TAP）,and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/m L in GM group and GMTI group,respectively（P〈0.05 vs. P-407）,and completely inhibited at 10.0 and 20.0 mg/m L（P〈0.01 vs. P-407）. After local injection of 10 mg/m L GMTI to rat leg muscular tissue,muscle fiber texture was normal,and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore,the expression of AMS,CRP and TAP was significantly increased in TP group as compared with control group（P〈0.01）,and significantly decreased in GM group as compared with TP group（P〈0.01）,and also slightly inhibited after 1.0 and 5.0 mg/m L GMTI treatment as compared with TP group（P〈0.05）,and significantly inhibited after 10.0 and 20.0 mg/m L GMTI treatment as compared with TP group（P〈0.01）. HE staining results demonstrated that pancreas cells were uniformly distributed in control group,and they were loosely arranged,partially dissolved,with deeply stained nuclei in TP group. Expectedly,after gradient GMTI treatment,pancreas cells were gradually restored to tight distribution,with slightly stained nuclei. This preliminary study indicated that GMTI could effectively inhibit pancreatic enzymes,and alleviate the severity of trauma-induced pancreatitis,and had a potential drug developing and clinic application value.展开更多
AIM: To evaluate the effi cacy of continuous regional arterial infusion therapy (CRAI) with gabexate mesilate and antibiotics for severe acute pancreatitis (SAP). METHODS: We conducted a prospective study on patients ...AIM: To evaluate the effi cacy of continuous regional arterial infusion therapy (CRAI) with gabexate mesilate and antibiotics for severe acute pancreatitis (SAP). METHODS: We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulf illed clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy (non-CRAI). CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate (2400 mg/d) was continuously administered for 3 to 5 d. The clinical outcome including serum infl ammation-related parameters were examined. RESULTS: The duration of abdominal pain in the CRAI group was 1.9 ± 0.26 d, whereas that in the non-CRAI group was 4.3 ± 0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared signifi cantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization signifi cantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4 ± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION: The present results suggest that CRAI using gabexate mesilate was effective against SAP.展开更多
基金supported by National Natural Science Foundation of China(No.81471682 and 81327003)
文摘Gabexate mesilate（GM） is a trypsin inhibitor,and mainly used for treatment of various acute pancreatitis,including traumatic pancreatitis（TP）,edematous pancreatitis,and acute necrotizing pancreatitis. However,due to the characteristics of pharmacokinetics,the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration,which is difficult to manage. Specially,when the blood supply of pancreas is directly damaged,intravenous administration is difficult to exert the optimum therapy effect. To address it,a novel thermosensitive in-situ gel of gabexate mesilate（GMTI） was developed,and the optimum formulation of GMTI containing 20.6%（w/w） P-407 and 5.79%（w/w） P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro,and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin（HE） staining,and its curative effect on grade Ⅱ pancreas injury was also evaluated by testing amylase（AMS）,C-reactive protein（CRP） and trypsinogen activation peptide（TAP）,and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/m L in GM group and GMTI group,respectively（P〈0.05 vs. P-407）,and completely inhibited at 10.0 and 20.0 mg/m L（P〈0.01 vs. P-407）. After local injection of 10 mg/m L GMTI to rat leg muscular tissue,muscle fiber texture was normal,and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore,the expression of AMS,CRP and TAP was significantly increased in TP group as compared with control group（P〈0.01）,and significantly decreased in GM group as compared with TP group（P〈0.01）,and also slightly inhibited after 1.0 and 5.0 mg/m L GMTI treatment as compared with TP group（P〈0.05）,and significantly inhibited after 10.0 and 20.0 mg/m L GMTI treatment as compared with TP group（P〈0.01）. HE staining results demonstrated that pancreas cells were uniformly distributed in control group,and they were loosely arranged,partially dissolved,with deeply stained nuclei in TP group. Expectedly,after gradient GMTI treatment,pancreas cells were gradually restored to tight distribution,with slightly stained nuclei. This preliminary study indicated that GMTI could effectively inhibit pancreatic enzymes,and alleviate the severity of trauma-induced pancreatitis,and had a potential drug developing and clinic application value.
基金Supported by Grant from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, No. 20590808The Research Committee of Intractable Diseases of the Pancreas, provided by the Ministry of Health, Labour, and Welfare Japan, No. 50253448
文摘AIM: To evaluate the effi cacy of continuous regional arterial infusion therapy (CRAI) with gabexate mesilate and antibiotics for severe acute pancreatitis (SAP). METHODS: We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulf illed clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy (non-CRAI). CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate (2400 mg/d) was continuously administered for 3 to 5 d. The clinical outcome including serum infl ammation-related parameters were examined. RESULTS: The duration of abdominal pain in the CRAI group was 1.9 ± 0.26 d, whereas that in the non-CRAI group was 4.3 ± 0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared signifi cantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization signifi cantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4 ± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION: The present results suggest that CRAI using gabexate mesilate was effective against SAP.
